The role of apoptosis in the pathogenesis of acute lung injury in rats

Objective: To investigate the potential role of apoptosis in the development of acute lung injury (ALI). Methods: Fortyeight Wistar rats were randomly divided into two groups .In ALI group,30 animals were intravenously infused with standard E.coli to reproduce the ALI model,and the samples were collected at 4,8 and 12 hours after bacterial challenge respectively.In sham operation group, 18 animals were intravenously infused with normal saline in equal volume and the samples were obtained at same intervals. The parameters of ALI including blood gas,lung index(LI), lung permeability index (LPI), tumor necrosis factorα (TNFα) and pulmonary pathology were determined. Apoptosis was detected by transmission electronmicroscopy, flow cytometry and TdT mediated dUTP nick end labeling (TUNEL), respectively. Results:It was observed that alveolar spaces were narrowed and neutrophils exuded at 4 h ours after E.coli challenge.With prolongation of time the pulmonary damage was worsened. PaO2 decreased, LI, LPI and TNFα increased,and the differences were significant between ALI group and sham operation group (all P<0.01). TUNEL results showed that in ALI group,a part of cells were positive,and apoptotic cells were (7.15±1.26)%,(12.39±1.67)%,(6.72±1.11)% at 4,8 and 12 hours, respectively, as detected by flow cytometry (all P<0.01). Conclusions: Apoptosis may play an important role in the pathogenesis of ALI. Apoptosis,as a pathogenetic mechanism, accelerates the inflammatory responses of ALI modulated by TNFα. With prolongation of ALI, apoptosis initially increased and then declined, keeping a low level.